Treatment of critical bleeding events in patients with immune thrombocytopenia: a protocol for a systematic review and meta-analysis.

BACKGROUND: Critical bleeding events in adults and children with ITP are medical emergencies; however, evidence-based treatment protocols are lacking. Due to the severe thrombocytopenia, (typically platelet count less than 20 × 109/L), a critical bleed portends a high risk of death or disability. We plan to perform a systematic review and meta-analysis of treatments for critical bleeding in patients with ITP that will inform evidence-based recommendations. METHODS: Literature searches will be conducted in four electronic databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. Eligible studies will be randomized controlled trials or observational studies that enrolled patients with ITP describing one or more interventions for the management of critical bleeding. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation will be conducted independently and in duplicate using Covidence and Excel. Outcomes will be pooled for meta-analysis where appropriate or summarized descriptively. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology will be used to evaluate the certainty of the evidence. Primary outcomes of interest will include frequency of critical bleeds, mortality and bleeding-related mortality, bleeding resolution, platelet count, and disability. DISCUSSION: Evidence-based treatments for critical bleeding in patients with ITP are needed to improve patient outcomes and standardize care in the emergency setting. SYSTEMATIC REVIEW REGISTRATION: CRD42020161206.

Dietary Elimination for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: The influence of diet on atopic dermatitis (AD) is complex, and the use of dietary elimination as a treatment has conflicting views. OBJECTIVE: To systematically review the benefits and harms of dietary elimination for the treatment of AD. METHODS: We searched MEDLINE, Embase, AMED, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to January 18, 2022, without language restrictions, for randomized controlled trials (RCTs) and observational studies comparing dietary elimination and no dietary elimination for the treatment of AD. We conducted random-effects meta-analyses of eczema outcomes. We used the grading of recommendations, assessment, development, and evaluation approach to assess certainty of evidence (CRD42021237953). RESULTS: Ten RCT (n = 599; baseline median of study mean age, 1.5 years; median of study mean SCOring Atopic Dermatitis index, 20.7, range, 3.5-37.6) were included in the meta-analysis. Compared with no dietary elimination, low-certainty evidence showed that dietary elimination may slightly improve eczema severity (50% with vs 41% without dietary elimination improved the SCOring Atopic Dermatitis index by a minimally important difference of 8.7 points, risk difference of 9% [95% CI, 0-17]), pruritus (daytime itch score [range, 0-3] mean difference, -0.21 [95% CI, -0.57 to 0.15]), and sleeplessness (sleeplessness score [range, 0-3] mean difference, -0.47 [95% CI, -0.80 to -0.13]). There were no credible subgroup differences based on elimination strategy (empiric vs guided by testing) or food-specific sensitization. Insufficient data addressed harms of elimination diets among included RCTs, although indirect evidence suggests that elimination diets may increase the risk for developing IgE-mediated food allergy. CONCLUSIONS: Dietary elimination may lead to a slight, potentially unimportant improvement in eczema severity, pruritus, and sleeplessness in patients with mild to moderate AD. This must be balanced against potential risks for indiscriminate elimination diets including developing IgE-mediated food allergy and withholding more effective treatment options for AD.

Long-term and serious harms of medical cannabis and cannabinoids for chronic pain: a systematic review of non-randomised studies.

OBJECTIVE: To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. STUDY SELECTION: Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. DATA EXTRACTION AND SYNTHESIS: A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for all meta-analyses and the Grades of Recommendations, Assessment, Development and Evaluation approach to evaluate the certainty of evidence. RESULTS: We identified 39 eligible studies that enrolled 12 143 adult patients with chronic pain. Very low certainty evidence suggests that adverse events are common (prevalence: 26.0%; 95% CI 13.2% to 41.2%) among users of medical cannabis for chronic pain, particularly any psychiatric adverse events (prevalence: 13.5%; 95% CI 2.6% to 30.6%). Very low certainty evidence, however, indicates serious adverse events, adverse events leading to discontinuation, cognitive adverse events, accidents and injuries, and dependence and withdrawal syndrome are less common and each typically occur in fewer than 1 in 20 patients. We compared studies with <24 weeks and ≥24 weeks of cannabis use and found more adverse events reported among studies with longer follow-up (test for interaction p<0.01). Palmitoylethanolamide was usually associated with few to no adverse events. We found insufficient evidence addressing the harms of medical cannabis compared with other pain management options, such as opioids. CONCLUSIONS: There is very low certainty evidence that adverse events are common among people living with chronic pain who use medical cannabis or cannabinoids, but that few patients experience serious adverse events.

Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review.

OBJECTIVE: To compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. DESIGN: Systematic review of randomised controlled trials (RCTs). DATA SOURCES: Medline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020. STUDY SELECTION AND REVIEW METHODS: RCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from -1.7% to -2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from -1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from -12.8% to -5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty). CONCLUSIONS: The reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD. PROSPERO REGISTRATION NUMBER: CRD42020179087.

Perioperative nonopioid analgesia reduces postoperative opioid consumption in knee arthroscopy: a systematic review and meta-analysis.

PURPOSE: The opioid epidemic has prompted an emphasis on investigating opioid-sparing alternatives for pain management following knee arthroscopy. This review evaluated the effects of perioperative nonopioid adjunct analgesia on postoperative opioid consumption and pain control in patients undergoing knee arthroscopy. METHODS: A systematic review and meta-analysis was performed using the following databases: PubMed, Embase, Web of Science, MEDLINE, and SCOPUS. Prospective comparative studies assessing the efficacy of various perioperative nonopioid analgesic strategies in patients undergoing knee arthroscopy were included. Twenty-five studies (n = 2408) were included. RESULTS: Pre-emptive nonopioid pain medications demonstrated a reduction in cumulative postoperative oral morphine equivalent (OME) consumption by 11.8 mg (95% CI - 18.3, - 5.4, p ≤ 0.0001) and VAS pain scores by 1.5 (95% CI - 2.3, - 0.7, p < 0.001) at 24 h compared to placebo. Postoperative nonopioid pain medications significantly reduced cumulative postoperative OME consumption by 9.7 mg (95% CI - 14.4, - 5.1, p < 0.001) and VAS pain scores by 1.0 (95% CI - 1.354, - 0.633, p < 0.001) at 24 h compared to placebo. Saphenous nerve blocks significantly reduced cumulative postoperative OME consumption by 6.5 mg (95% CI - 10.3, - 2.6, p = 0.01) and VAS pain scores by 0.8 (- 1.4, - 0.3, p = 0.03) at 24 h compared to placebo. Both preoperative patient education and postoperative cryotherapy reduced postoperative opioid consumption. CONCLUSION: Perioperative nonopioid pharmacotherapy, saphenous nerve blocks, and cryotherapy for patients undergoing knee arthroscopy significantly reduce opioid consumption and pain scores when compared to placebo at 24 h postoperatively. These interventions should be considered in efforts to reduce opioid consumption in patients undergoing knee arthroscopy. More research is needed to determine which interventions can reduce pain outside of the immediate postoperative period and the potential synergistic effects of combining interventions. LEVEL OF EVIDENCE: II.